PROJECT SUMMARY Advances in understanding the molecular basis of leukemia, together with the wealth of emerging innovative pharmaceutical compounds, have brought great opportunities to improve the clinical outcome of patients. To maximize the value of these discoveries, it is imperative to demonstrate our ability to molecularly characterize individual tumors and apply this information to enroll patients onto therapeutic protocols that match distinct molecular profiles to specific targeting treatments?all within the context of an effective cancer therapeutic trials' system. To create an atmosphere for both research creativity and rapid clinical translation of novel discoveries into treatment approaches of adult leukemia patients, the Alliance for Clinical Trials in Oncology (hereafter called Alliance) Leukemia Correlative Science Committee (A-LCSC), and the SWOG Leukemia Translational Medicine Subcommittee (S-LTMS) and the Broad Institute have elected to joined forces in 2014 and created an Integrated Translational Science Center for Leukemia (ITSC-L). The overall goal of the ITSC-L is to identify the genetic and molecular aberrations that characterize leukemic transformation, understand their contribution to therapeutic response or resistance, and utilize this information for the design of rational therapeutic trials that match specific molecular aberrations to emerging targeted therapies. These goals will be achieved through the carefully selection of Pilot Studies that involve outstanding investigators working within Alliance and SWOG and those working outside the groups. Ultimately, these efforts should not only result in a significant improvement in the clinical outcome for leukemia patients, but are expected to generate cutting-edge findings applicable to other types of cancer. The Specific Aims of this Program are the following: Specific Aim 1. To maintain an Integrated Translational Science Center for Leukemia (ITSC-L) that will promote research among investigators working within the NCI National Clinical Trials Network (NCTN) system and outside the system by providing and coordinating funding, expertise, technology, tissue and data for innovative studies with clinical relevance; Specific Aim 2. To identify novel prognostic and predictive genetic and epigenetic markers and therapeutic targets for the development of innovative therapeutic paradigms that transform the current approach to leukemia patients and improve their cure rate; Specific Aim 3. To rapidly integrate high impact correlative science into early and late phase therapeutic trials of leukemia supported by the NCTN.